|
NISCAIR ONLINE PERIODICALS REPOSITORY (NOPR) >
NISCAIR PUBLICATIONS >
Research Journals >
Indian Journal of Chemistry -Section B (IJC-B) >
IJC-B Vol.45B [2006] >
IJC-B Vol.45B(02) [February 2006] >
| Title: | Quantitative structure activity relationship studies of diarylimidazoles as selective COX-2 inhibitors |
| Authors: | Yadav, M R
Puntambekar, D S
Sarathy, K P
Vengurlekar, S
Giridhar, R |
| Keywords: | QSAR
COX-2 inhibitors
diarylimidazole |
| Issue Date: | Feb-2006 |
| Publisher: | CSIR |
| IPC Code: | Int.Cl.7 C 07 D |
| Abstract: | Quantitative structure activity relationship approach using stepwise regression analysis has been applied to a series of 63 diarylimidazole derivatives as selective COX-2 inhibitors. For this purpose 49 compounds have been taken as training set and the rest as test set. These studies have produced good predictive models with high regression constant (r = 0.927), low standard deviation (0.279) and standard error of regression (0.30). A good correlation of various parameters like hydrophobicity ( ), electrophilicity (σ) and van der Waal’s volume of various substituents has been established with COX-2 inhibitory activity. The impact of these structural parameters on the selectivity ratio (log COX-1/COX-2) has also been analyzed. The resulting correlation revealed that substitution at position A3 with groups having low van der Waal’s volume and high and σ values and substitution at A5 and A4 with groups having high and σ values are significant in increasing COX-2 inhibitory activity. Parameters for COX-2 enzyme selectivity have also been identified and on the basis of obtained correlation certain new compounds have been designed with much higher selectivity as COX-2 enzyme inhibitors in comparison to compounds reported in literature with retention of high inhibitory potency. |
| Page(s): | 475-482 |
| ISSN: | 0975-0983(Online); 0376-4699(Print) |
| Source: | IJC-B Vol.45B(02) [February 2006]
|
|
